Contribution of the sodium-calcium exchanger to contractions in immature rabbit ventricular myocytes.

In immature cardiac myocytes, the sarcoplasmic reticulum is sparse. Thus, we hypothesized that sarcolemmal Ca2+ influx through Na(+)-Ca2+ exchange is the dominant mechanism for modulating intracellular Ca2+ during contractions in fetal and neonatal hearts. We measured Na(+)-Ca2+ exchange currents in neonatal and adult rabbit ventricular cells using a rapid solution switch into 0 mM external Na+. The current densities (mean +/- SEM) were larger in 8 neonatal cells than in 10 adult cells (5.4 +/- 1.38 versus 1.65 +/- 0.25 pA/pF). Intracellular Ca2+ transients after inhibiting the sarcoplasmic reticulum with ryanodine and thapsigargin were unchanged in 15 neonatal cells, but decreased in 15 adult cells to 78.9 +/- 5.6% of baseline. When the Ca2+ channels were also inhibited by adding nifedipine, Ca2+ transients from Na(+)-Ca2+ exchange were 30.0 +/- 3.5% of baseline in neonatal cells compared with 13.4 +/- 3.4% in adult cells. Simultaneous contractions were a larger percent of baseline in neonatal cells (85.7.6 +/- 6.4%) than in adult cells (78.9 +/- 5.6%) after inhibiting the sarcoplasmic reticulum, and were unmeasureable in many cells from both age groups after inhibiting the Ca2+ channels as well. The ratio of Na(+)-Ca2+ exchanger mRNA to sarcoplasmic reticulum Ca(2+)-ATPase mRNA levels decreased from 1.0 +/- 0.13 to 0.4 +/- 0.03 to 0.26 +/- 0.02 in fetal, neonatal and adult ventricles, respectively. These measurements were consistent with a dominant role for the Na(+)-Ca2+ exchanger in the immature heart.

Association study of schizophrenia with dopamine D3 receptor gene polymorphisms: probable effects of family history of schizophrenia?

Using a case-control design, a reported association of schizophrenia with homozygosity at the dopamine D3 receptor gene locus was investigated in a group of patients (n = 53), with schizophrenia (DSM-III-R), and psychiatrically normal controls (n = 61), matched for ethnicity and area of residence. No significant differences in the distribution of alleles or genotypes between the two groups could be detected. However, among patients with a family history of schizophrenia, as compared to controls without such family history, an association with allele 1 at this locus was noted (Odds ratio 12.4, C.I. 1.61, 96.35).

The use of the 99mTc-pertechnetate neck/thigh ratio as a test of thyroid function.

A total of 100 patients were studied by standard thyroid function tests and the 99mTc-pertechnetate neck/thigh ratio was determined. This ratio or "trapping index" correlated closely with 131I uptake. The 99mTc test should be followed by scanning at 20 minutes to distinguish diffuse from localized thyroid disease. TSH stimulation and suppression studies can be done. It is recommended that this ratio be used in place of the standard 24-hour RAIU study, as it gives the same information at a saving in time, money, and radiation exposure.

Calcitonin resistance: clinical and immunologic studies in subjects with Paget's disease of bone treated with porcine and salmon calcitonins.

15 patients with Paget's bone disease were treated with varying schedules of porcine (3.8-157.5 MRCU/kg per wk) and/or salmon (1.5-210 MRCU/kg per wk) calcitonins over periods ranging from 4 to 24 months. All of the subjects experienced a striking decrease in serum alkaline phosphatase during the first 4 months of treatment. In six patients, however, resistance to these peptides was suggested by a subsequent elevation of alkaline phosphatase activity in spite of continued and augmented hormone administration. These rebounds in alkaline phosphatase levels correlated with the appearance of calcitonin-binding substances and neutralizing material in serum. Incubations of calcitonins-(125)I and sera from these six subjects resulted in the association of radioactivity with material whose behavior on chromatoelectrophoresis (6/6), sucrose density ultracentrifugation and immunoelectrophoresis (one subject) was identical with that of 7S immunoglobulin. Specific, reversible in vitro binding of salmon calcitonins-(125)I was observed in sera obtained from these patients 5 to 12 months after initiation of salmon calcitonin therapy. All six of these subjects' sera acquired the capacity to neutralize salmon calcitonin's hypocalcemic effect in rat bioassay. Neutralization titers correlated with maximal binding capacities, which ranged from 0.042 to 6.6 mg/liter of serum. Competitive displacement of calcitonins-(125)I from the sera of one patient treated with both porcine and salmon calcitonin indicated separate populations of antibodies to these hormones. In spite of return of disease activity comparable to baseline levels, 3/5 resistant subjects treated with salmon calcitonin failed to develop hypocalcemia after injection of 300-1000 MRCU of salmon calcitonin, but two of these patients developed hypocalcemia in response to the porcine hormone. The disappearance of total radioactivity from the circulation after intravenous administration of salmon calcitonin-(125)I was retarded and the amount of serum radioactivity precipitable in 50% (NH(4))(2)SO(4) greater in 3/3 resistant patients compared to control subjects. These observations on the incidence of significant titers of neutralizing antibodies to salmon (40%) and porcine (66%) calcitonins during their chronic (> 4 months) administration to man clearly indicate that an appraisal of this possibility be included in studies involving protracted use of these hormones.